title: The yeast AMPK homolog SNF1 regulates acetyl coenzyme A homeostasis and histone acetylation.
abstract: Acetyl coenzyme A (acetyl-CoA) is a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription. Concentration of acetyl-CoA affects histone acetylation and links intermediary metabolism and transcriptional regulation. Here we show that SNF1, the budding yeast ortholog of the mammalian AMP-activated protein kinase (AMPK), plays a role in the regulation of acetyl-CoA homeostasis and global histone acetylation. SNF1 phosphorylates and inhibits acetyl-CoA carboxylase, which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in the de novo synthesis of fatty acids. Inactivation of SNF1 results in a reduced pool of cellular acetyl-CoA, globally decreased histone acetylation, and reduced fitness and stress resistance. The histone acetylation and transcriptional defects can be partially suppressed and the overall fitness improved in snf1Δ mutant cells by increasing the cellular concentration of acetyl-CoA, indicating that the regulation of acetyl-CoA homeostasis represents another mechanism in the SNF1 regulatory repertoire.
authors.affiliation: Department of Biological Sciences, St. John's University, Queens, New York, USA.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.forename: Luciano
authors.initials: L
authors.lastname: Galdieri
authors.forename: Ales
authors.initials: A
authors.lastname: Vancura
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics; D063185:Epigenetic Repression; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006706:Homeostasis; D008316:Malonyl Coenzyme A / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000254:growth & development; D013312:Stress, Physiological
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; D021901:DNA, Intergenic; D006657:Histones; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D051548:Histone Acetyltransferases; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D006655:Histone Deacetylases; D003066:Coenzyme A Ligases; C561832:Acsl1 protein, rat